Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)

Abstract

Alzheimer’s disease (AD) is characterized by progressive dysfunction of memory and higher cognitive functions with abnormal accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles throughout cortical and limbic brain regions. At present no curative treatment is available, and research focuses on drugs for slowing disease progression or providing prophylaxis. Withania somnifera (WS) also known as ‘ashwagandha’ is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is a paucity of data on the potential neuroprotective effects of W.somnifera against β-Amyloid (1–42)-induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of methanol:Chloroform (3:1) extract of ashwagandha against β-amyloid induced toxicity and HIV-1Ba-L (clade B) infection using a human neuronal SK-N-MC cell line. Our results showed that β-amyloid induced cytotoxic effects in SK-N-MC cells as shown by decreased cell growth when tested individually. Also, confocal microscopic analysis showed decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC cells compared to uninfected cells. However, when ashwagandha was added to β-amyloid treated and HIV-1 infected samples, the toxic effects were neutralized. Further, the MTT cell viability assays and the peroxisome proliferator-activated receptor-γ (PPARγ) levels supported these observations indicating the neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.

Effects of Ashwagandha (Roots of <i>Withania somnifera</i>) on Neurodegenerative Diseases

“…Further studies of Ashwagandha will probably contribute to resolving an urgent unmet medical need: efficacious treatments that may offer cure of neurodegenerative diseases. 17) Memory improvement 38) Neuroprotective effects in vitro 33,35) Aβ clearance in vivo 38) Withanolide A Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 21) Memory improvement 21) Upregulation of BACE1, ADAM10 and IDE in vitro 31) Withanoside IV Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 22) Memory improvement 22) Withanoside VI Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 23) Memory improvement 23) Sominone Axonal regeneration and synaptic reconstruction in vitro 22) Axonal growth in vivo 28) Memory improvement 27) and memory enhancement 28) Denosomin Axonal regeneration and neuroprotective effect in vitro 45) Withanone Neuroprotective effects in vitro 35) Spinal cord injury Withanoside IV Axonal growth in vivo and functional recovery 43) Denosomin Axonal growth in vivo and functional recovery 45) Parkinson's disease Extract Anti-oxidant effect in vivo [55][56][57][58][59] Neuroprotective effect in vivo 55,59) Functional recovery [55][56][57][58][59] Huntington's disease Extract Anti-oxidant ef...…”

“…Kurapati et al 33) investigated effects of methanol-chloroform (3 : 1) extract of Ashwagandha against Aβ1-42-induced toxicity in cultured human neuroblastoma SK-N-MC cells. Aβ1-42 induced cell death and internalization of Aβ1-42.…”

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer’s disease

“…Thus, although BtAcOEt is a fraction derivate from BtHA, it is also the direct result of removing the most polar fraction from the whole crude extract. In this way, as many reports indicate (Lin et al 2007;Deharo and Ginsburg 2011;Rosoanaivo et al, 2011), it is well known fact in phytochemistry that crude plant extracts, that include multiple and diverse compounds (Kurapati et al 2013), are usually more powerful medicines than pure isolated compounds. This effect may be due to the multiple actions of complex mixtures, but could also arise from synergistic interactions among their components (Fernandez et al 2005).…”

Reducing Aβ load and tau phosphorylation: Emerging perspective for treating Alzheimer's disease

“…Research has demonstrated that in an in vitro condition, ashwagandha regenerates damaged axons, dendrites, and synapses (Kuboyama et al, 2005;Kurapati et al, 2013).…”